P590: MODIFICATIONS IN PRIMARY HEMOSTASIS AS ADDITIONAL RISK FACTORS OF BLEEDING IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML): UKRAINIAN PROSPECTIVE STUDY IN A REAL-LIFE COHORT.
Authors: Zinaida Stupakova, Iryna Dyagil, Zoya Martina, Anna Sergeieva, Oksana Karnabeda, Ulyana Melnyk, Olga Novosad, Stanislav Rushkovsky
Journal: HemaSphere (2023)

Background: Bleeding is one of the most common reasons of early mortality and severe treatment complications in patients with AML. Prediction of bleeding in these cohort of patients become increasingly relevant as well as looking for new risk factors remain meaningful1. Aims: The primary endpoints were a qualitative and quantitative functions of plasma von Willebrand factor (vWF) which include measurements of vWF activity (vWF:ristocetin cofactor [vWF:RCo]), vWF level (vWF:antigen [vWF:Ag]), factor VIII coagulation activity regarding to vWF(vWF:FVIII) and FVIII activity (FVIII) as an additional bleeding risk factor in newly diagnosed AML patients. Methods: 48 patients with newly diagnosed AML (excluded APL) were included in the study group (25 males and 23 females; median age: 52,5 years). The diagnosis of AML established by FAB and WHO classification systems and the plasma samples were collected before the beginning of induction therapy. The grade (G) of bleeding events was assessed according to Modified WHO Bleeding Scale (WHO BS). Control group included 20 age-matched and sex-matched healthy individuals. Levels of vWF:Ag and vWF:RCo tested on automated latex particle-enhanced immunoassay ACL Elite Pro and ACL TOP 300 (Instrumentation Laboratory). vWF:FVIII and FVIII were measured using a clotting assay by fully automated coagulometer ACL Elite Pro (Instrumentation Laboratory). Results: In our study group 44,9 % patients were experienced bleeding events (G1-4) before and during the first course of treatment whereas there were no bleeding episodes in the control group (G0). The median platelets in the study group was 41,5 (IQR, 27,5 - 73) versus 260 (IQR, 154 - 199) in the control group (p<0,05). Thrombocytopenia of (I-IV grade) was associated with rough bleeding in patients with AML compared to the control group (p=0,001). Further, there was no statistically significant difference between grade of thrombocytopenia and severity of bleeding (G0-4) or values of vWF in patients with AML. Decline rate vWF:Ag had been observed in eight patients with AML (16%) and was associated with rough bleeding (G2-4) compared to patients who had normal vWF:Ag (p=0.03). vWF:Ag levels (median 125,5) were elevated in 37% of patients in the main group and can be related to the inflammatory response as an acute phase protein. vWF:RCo below normal ranges was observed in eleven patients (22%) with AML. Among them the most frequent bleeding events were G2 (6/11) and G4 (3/11), three of them died during the first course of chemotherapy due to gastrointestinal and cranial bleeding. Therefore, we found a statistically significant association between a decreased levels of vWF:RCo below normal ranges and the occurrence of severe bleeding episodes (G2-G4) in patients with AML compared with the group that had normal ranges of vWF:RCo and no bleeding episodes (G0) (p>0,001). Low vWF:FVIII and FVIII levels in patients with AML and bleeding episodes G2-G4 as well as other values had statistic difference to the patients with no bleeding events (G0) (p=0,03). Summary/Conclusion: Due to the results of our study features of vWF may well become a promising accessory risk factors of rough bleeding in AML and become an excellent addition to already existing scales as well as one of important tools in a new bleeding scale establishment. 1 J. Versluis, M. Pandey, Y. Flamand et al. Prediction of life-threatening and disabling bleeding in patients with AML receiving intensive induction chemotherapy. Blood Adv. (2022) 6 (9): 2835–2846.Keywords: von Willebrand factor (vWF), AML, Bleeding